Function of Laccases in Anopheles gambiae

描述（申请人提供）：项目概述：漆酶是一种含铜氧化酶，具有广泛的底物特异性。它们参与植物和真菌的多种生理过程，包括木质素的合成和降解、形态发生、色素沉着、解毒和毒力。相关的多铜氧化酶参与保护细菌和真菌免受金属毒性。漆酶在昆虫中是否具有类似的功能尚不清楚，因为以前没有详细研究过昆虫中的漆酶。昆虫漆酶的一个确定的作用是催化角质层鞣制和硬化反应，但初步结果表明，一些昆虫漆酶基因可能有其他功能。本研究的长期目标是确定六种假定的漆酶在蚊子中的功能，以增加我们对漆酶-底物相互作用的理解，并最终利用这些信息来制定减少蚊子传播疾病的策略。该项目有三个具体目标，旨在测试关于漆酶在蚊子生理学中的潜在功能的假设，并研究用于漆酶功能的生化分析的漆酶抑制剂，以及测试漆酶是否可能是化学防治蚊子的潜在有用的新靶标。1)研究漆酶在角质层硬化、色素沉着、伤口愈合和蛋壳鞣制中的作用。2)确定漆酶是否在保护昆虫免受有毒物质如幼虫环境中的酚类化合物或血粉中的铁的影响方面发挥作用。3)设计、合成和测试按蚊漆酶抑制剂，探索漆酶活性位点，并测试抑制剂对蚊子生长发育和存活的影响。相关性：由于蚊子是人类疾病的传播媒介，它们对人类健康有着巨大的影响，而冈比亚按蚊作为非洲疟疾的主要传播媒介尤为重要。对蚊子漆酶的研究将增加我们对蚊子生物学基本过程的理解，并可能提供有关这些昆虫如何传播疾病或如何耐受有毒化学物质的知识。破坏漆酶功能可能为控制蚊子种群提供新的机制。

DESCRIPTION (provided by applicant): Project summary: Laccases are copper-containing oxidases with broad substrate specificity. They have been implicated in a variety of physiological processes in plants and fungi, including lignin synthesis and degradation, morphogenesis, pigmentation, detoxification, and virulence. Related multicopper oxidases are involved in protection against metal toxicity in bacteria and fungi. Whether laccases have similar functions in insects is unknown, as laccases have not previously been investigated in insects in detail. The one identified role of insect laccases is in catalyzing cuticle tanning and sclerotization reactions, but preliminary results suggest that some insect laccase genes may have other functions. The long term goals of this research are to determine the function of six putative laccases in the mosquito, Anopheles garnbiae, to increase our understanding of laccase-substrate interactions, and eventually to use this information to develop strategies to reduce disease transmission by mosquitoes. This project has three specific aims designed to test hypotheses regarding potential functions for laccases in mosquito physiology and to investigate laccase inhibitors for use in biochemical analyses of laccase function and for testing whether laccases may be a potentially useful new target for chemical control of mosquitoes. 1) Investigate the role of laccases in cuticle sclerotization, pigmentation, wound healing, and egg shell tanning. 2) Determine whether laccases have a role in protecting insects from toxic substances such as phenolic compounds in the larval environment or iron in the blood meal. 3) Design, synthesize, and test inhibitors of Anopheles laccases for exploring the laccase active site and for tests of the inhibitors' effects on mosquito development and survival. Relevance: Because they are vectors of human diseases, mosquitoes have a tremendous human health impact, and Anopheles gambiae is particularly important as the major vector of malaria in Africa. Studies of mosquito laccases will increase our understanding of fundamental processes in mosquito biology and may provide knowledge regarding how these insects transmit diseases or how they tolerate toxic chemicals. Disrupting laccase function may provide a new mechanism for controlling mosquito populations.